Document Detail

Eosinophils are necessary for pulmonary arterial remodeling in a mouse model of eosinophilic inflammation-induced pulmonary hypertension.
MedLine Citation:
PMID:  21908591     Owner:  NLM     Status:  MEDLINE    
There is increasing evidence that inflammation plays a pivotal role in the pathogenesis of some forms of pulmonary hypertension (PH). We recently demonstrated that deficiency of adiponectin (APN) in a mouse model of PH induced by eosinophilic inflammation increases pulmonary arterial remodeling, pulmonary pressures, and the accumulation of eosinophils in the lung. Based on these data, we hypothesized that APN deficiency exacerbates PH indirectly by increasing eosinophil recruitment. Herein, we examined the role of eosinophils in the development of inflammation-induced PH. Elimination of eosinophils in APN-deficient mice by treatment with anti-interleukin-5 antibody attenuated pulmonary arterial muscularization and PH. In addition, we observed that transgenic mice that are devoid of eosinophils also do not develop pulmonary arterial muscularization in eosinophilic inflammation-induced PH. To investigate the mechanism by which APN deficiency increased eosinophil accumulation in response to an allergic inflammatory stimulus, we measured expression levels of the eosinophil-specific chemokines in alveolar macrophages isolated from the lungs of mice with eosinophilic inflammation-induced PH. In these experiments, the levels of CCL11 and CCL24 were higher in macrophages isolated from APN-deficient mice than in macrophages from wild-type mice. Finally, we demonstrate that the extracts of eosinophil granules promoted the proliferation of pulmonary arterial smooth muscle cells in vitro. These data suggest that APN deficiency may exacerbate PH, in part, by increasing eosinophil recruitment into the lung and that eosinophils could play an important role in the pathogenesis of inflammation-induced PH. These results may have implications for the pathogenesis and treatment of PH caused by vascular inflammation.
M Weng; D M Baron; K D Bloch; A D Luster; J J Lee; B D Medoff
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-09
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  301     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-06     Completed Date:  2012-02-10     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L927-36     Citation Subset:  IM    
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MeSH Terms
Adiponectin / genetics,  metabolism
Antibodies / pharmacology,  therapeutic use
Cell Extracts / pharmacology
Cell Proliferation
Cells, Cultured
Chemokine CCL11 / genetics,  metabolism,  secretion
Chemokine CCL2 / genetics,  metabolism
Chemokine CCL24 / genetics,  metabolism,  secretion
Disease Models, Animal
Eosinophils / pathology*
Gene Knockout Techniques
Hypertension, Pulmonary / etiology,  pathology*,  prevention & control
Interleukin-5 / antagonists & inhibitors
Lung / metabolism,  pathology
Macrophages / secretion
Mice, Inbred C57BL
Mice, Knockout
Mitogens / pharmacology
Myocytes, Smooth Muscle / drug effects
Primary Cell Culture
Pulmonary Artery / pathology*
Pulmonary Eosinophilia / chemically induced,  complications*
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/Adiponectin; 0/Antibodies; 0/Ccl11 protein, mouse; 0/Ccl2 protein, mouse; 0/Ccl24 protein, mouse; 0/Cell Extracts; 0/Chemokine CCL11; 0/Chemokine CCL2; 0/Chemokine CCL24; 0/Interleukin-5; 0/Mitogens; 9006-59-1/Ovalbumin

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